An urgent need for new antiretroviral compounds has become evident as more people worldwide are exposed to and become infected with HIV. The efficacy of pre- and post-exposure treatment with the antiviral compound (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) was tested against simian immunodeficiency virus infection of macaques as a model for HIV. PMPA was administered subcutaneously once daily beginning either 48 hours before, 4 hours after, or 24 hours after infection. Treatment continued for 4 weeks, and the virologic, immunologic, and clinical status of the macaques has been monitored. PMPA prevented SIV infection in all macaques without toxicity, whereas all control macaques became infected. This study represents the first description of an antiviral compound that prevents AIDS virus infection when given after exposure to the virus. Currently, post-exposure prophylaxis with AZT against HIV is widely accepted and used in humans despite numerous reports of failure. Post-exposure prophylaxis with PMPA could have a significant impact on preventing HIV infection in health care workers or others accidentally exposed to the virus. Foamy retroviruses have been isolated from numerous mammalian species, they are not known to be associated with any known disease. The proteins of this distinct class of retroviruses have not been characterized; an examination of the DNA sequence data available suggests that these viruses may not contain the zinc finger in the nucleocapsid protein which is ubiquitous in all other retroviruses. The zinc finger consists of a highly conserved array of amino acids which bind zinc; deletions in that array lead to non-infectious virions. We have obtained an isolate of foamy retrovirus from a baboon that replicates to unusually high titers in a variety of fibroblast cell lines. Virus has been produced and is being analyzed by high pressure liquid chromatography to determine the amino composition of the viral proteins. The availability of purified viral and protein preparations will also permit screening of human and non-human primate populations for antibodies to these viral proteins and to further examine any possible association with disease.